Biology subjects

Wallmann, A.

Publications and source records attributed to Wallmann, A..

3 recordsLinked to original sources

bioRxiv2025

p53 status determines the epigenetic response to demethylating agents Azacitidine and Decitabine.

5-Azacitidine (Aza) and 5-Aza-2-deoxycytidine (Dac) are widely used demethylating drugs that directly integrate into nucleic acids. They are frequently used interchangeably, surprisingly as their selectivity is unique from the other, with no predictors of response or clinical biomarkers to indicate drug preference. Using these drugs to induce demethylation, we combine DRIPc-Seq, Immunostaining, RNA-Seq and Mass spectrometry to uncover unique cellular responses. Activation of p53, exclusively by Aza, sustained accumulation of R-loops in CpG islands of p53 target genes. This effect was abolished by the removal of p53, compounded by destabilisation of heterochromatin marks. Dac treatment induced global chromatin modification, sustaining DNA damage, which was heightened in the absence of p53. Rescue experiments reversed the changes observed in the epigenome, demonstrating a direct role for p53 in preserving H3K9me3 and H3K27me3. These insights further our knowledge of how cells recognize and respond to methylation changes and uncover novel roles for p53 in modulation of the epigenome. Further to this, we determine a first in kind biomarker in p53 status that may be relevant for clinical settings.

molecular biology↗

bioRxiv2024

Structural and evolutionary determinants of Argonaute function

Members of the Argonaute protein superfamily adopt functions ranging from host-defense to mediating elaborate and multi-component post-transcriptional and epigenetic systems of control. Despite this diversity of biological roles, the Argonaute structural fold is highly conserved throughout all domains of life. This raises questions about how Argonautes evolved to adapt to this increasing complexity of function, while conserving features that are broadly shared across the phylogenetic tree. Integrating structural, sequence, phylogenetic data and disease-related mutational data, we compiled a comprehensive study of the Argonaute evolutionary trajectory. By comparing Argonaute proteins across a diverse set of lineages and extensive evolutionary timescale, we identified universal and clade-specific sequence signatures and intra-protein contact networks that underlie the Argonaute structural fold, nucleic acid interface and protein-protein binding sites. We analyze how these features are affected by disease-related mutations and are fundamentally altered in the case of the Argonaute-like Med13 protein. With this work we gain better insights into how Argonaute function diversified in eAgos by redrawing the emergence of conserved molecular features that are associated with new biological functions.

bioinformatics↗

bioRxiv2018

A molecular mechanism for salt stress-induced microtubule array formation in Arabidopsis

Microtubules are filamentous structures necessary for cell division, motility and morphology, with dynamics critically regulated by microtubule-associated proteins (MAPs). We outline the molecular mechanism by which the MAP, COMPANION OF CELLULOSE SYNTHASE1 (CC1), controls microtubule bundling and dynamics to sustain plant growth under salt stress. CC1 contains an intrinsically disordered N-terminus that links microtubules at evenly distributed distances through four conserved hydrophobic regions. NMR analyses revealed that two neighboring residues in the first hydrophobic binding motif are crucial for the microtubule interaction, which we confirmed through live cell analyses. The microtubule-binding mechanism of CC1 is remarkably similar to that of the prominent neuropathology-related protein Tau, indicating evolutionary convergence of MAP functions across animal and plant cells.

cell biology↗